Stobadine – An Indole Type Alternative to the Phenolic Antioxidant Reference Trolox

Juránek, Ivo; Račková, Lucia; Štefek, Milan

doi:10.5772/32784

Cited by 6 publications

(7 citation statements)

References 33 publications

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“…Novel substituted hexahydropyridoindoles, designed as substitution derivatives of the antioxidant drug stobadine, [1][2][3][4] were recently synthesized and characterized as efficient chain-breaking antioxidants. [5][6][7] Modification of the stobadine molecule by aromatic electron-donating substitution was reported to enhance the intrinsic free radical scavenging activity, while variations of the N2 substituent afforded a synthetically accessible way to modulate the biological availability by affecting both lipophilicity and basicity of the molecule, without changing significantly the free radical scavenging activity.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant action of the hexahydropyridoindole SMe1EC2 in the cellular system of isolated red blood cellsin vitro

et al. 2013

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Objectives: The subject of this study was the hexahydropyridoindole compound SMe1EC2 with reported antioxidant and neuroprotective effects and low toxicity. In this study, the antioxidant action of SMe1EC2 was investigated in a greater detail in the system of isolated rat erythrocytes. Methods: First, the compound was subjected to the DPPH test. Second, the overall antioxidant action of the compound was studied in the cellular system of isolated rat erythrocytes oxidatively stressed by free radicals derived from either the hydrophilic azoinitiator AAPH or the lipophilic t-BuOOH, and compared with reference antioxidants.Results: The DPPH test revealed significant antiradical activity of SMe1EC2 comparable with that of the standard trolox. In the cellular system, SMe1EC2 protected red blood cells against free radical-initiated hemolysis. The overall antioxidant efficacy of SMe1EC2 relative to the reference antioxidant stobadine was strongly affected by the lipophilicity of the initiating free radical species. Conclusions: The results proved high antiradical efficacy of SMe1EC2. In the system of t-BuOOH/isolated erythrocytes, a model cellular system of endogenously generated peroxyl radicals, SMe1EC2 significantly exceeded the parent stobadine in its antioxidant action. Considering the reported results of preclinical studies of SMe1EC2 showing its profound neuroprotective effects and low toxicity, the compound represents an example of a potential pharmacologically practicable antioxidant drug.

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Section: Introductionmentioning

confidence: 99%

Antioxidant action of the hexahydropyridoindole SMe1EC2 in the cellular system of isolated red blood cellsin vitro

et al. 2013

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“…The potent pyridoindole antioxidant and free radical scavenger, stobadine, deferred the progression of streptozocin-induced diabetic cataract in Wistar rats by blocking lipid peroxidation, in vivo [171,177]. In other studies, the endogenous free radical scavenger, melatonin, attenuated BSO-induced cataract formation in neonatal rats in vivo and enhanced total lenticular GSH content, suggesting that either the free radical scavenging and/or a stimulatory effect on GSH content was responsible for the anti-cataract activity [178].…”

Section: Typical Antioxidantsmentioning

confidence: 99%

Current Trends in the Pharmacotherapy of Cataracts

et al. 2020

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Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies improve, the number of people affected with cataracts is predicted to increase worldwide, especially in low-income nations with limited access to surgery. Although cataract surgery is considered safe, it is associated with some complications such as retinal detachment, warranting a search for cheap, pharmacological alternatives to the management of this ocular disease. The lens is richly endowed with a complex system of non-enzymatic and enzymatic antioxidants which scavenge reactive oxygen species to preserve lens proteins. Depletion and/or failure in this primary antioxidant defense system contributes to the damage observed in lenticular molecules and their repair mechanisms, ultimately causing cataracts. Several attempts have been made to counteract experimentally induced cataract using in vitro, ex vivo, and in vivo techniques. The majority of the anti-cataract compounds tested, including plant extracts and naturally-occurring compounds, lies in their antioxidant and/or free radical scavenging and/or anti-inflammatory propensity. In addition to providing an overview of the pathophysiology of cataracts, this review focuses on the role of various categories of natural and synthetic compounds on experimentally-induced cataracts.

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“…The indole scaffold, found in numerous natural and synthetic substances, is considered a useful structural subunit for drug design and discovery [ 26 , 27 , 28 , 29 , 30 ]. In our pursuit of multifactorial drugs to treat diabetic complications we were inspired by both an efficient antioxidant and free radical scavenging agent, stobadine (STB, 1a ) [ 25 , 31 , 32 , 33 , 34 , 35 ], a drug of hexahydropyridoindole nature, and by the highly efficient ARI lidorestat, derivative of indol-1-yl acetic acid [ 36 ]. Accordingly, both tetrahydropyridoindole scaffold evolved from stobadine, and indol-1-yl acetic acid moiety were used in our lab during the last 15 years as starting fragments in developing of several promising series of aldose reductase inhibitors/antioxidants.…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

et al. 2021

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Aldose reductase (AR, ALR2), the first enzyme of the polyol pathway, is implicated in the pathophysiology of diabetic complications. Aldose reductase inhibitors (ARIs) thus present a promising therapeutic approach to treat a wide array of diabetic complications. Moreover, a therapeutic potential of ARIs in the treatment of chronic inflammation-related pathologies and several genetic metabolic disorders has been recently indicated. Substituted indoles are an interesting group of compounds with a plethora of biological activities. This article reviews a series of indole-based bifunctional aldose reductase inhibitors/antioxidants (ARIs/AOs) developed during recent years. Experimental results obtained in in vitro, ex vivo, and in vivo models of diabetic complications are presented. Structure–activity relationships with respect to carboxymethyl pharmacophore regioisomerization and core scaffold modification are discussed along with the criteria of ‘drug-likeness”. Novel promising structures of putative multifunctional ARIs/AOs are designed.

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Stobadine – An Indole Type Alternative to the Phenolic Antioxidant Reference Trolox

Cited by 6 publications

References 33 publications

Antioxidant action of the hexahydropyridoindole SMe1EC2 in the cellular system of isolated red blood cellsin vitro

Antioxidant action of the hexahydropyridoindole SMe1EC2 in the cellular system of isolated red blood cellsin vitro

Current Trends in the Pharmacotherapy of Cataracts

Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

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